This competing renewal application proposes to continue the follow-up study of 800 families enrolled in the Center's prospective investigations into the etiology of substance use disorder (SUD). Proband fathers are ascertained on the basis of the presence or absence of SUD, and have a biological son or daughter between 10-12 years of age at baseline. Ascertainment criterion for SUD probands is a lifetime diagnosis (abuse or dependence) on any illegal compound or a compound consumed without medical prescription. The children of SUD men are assigned to the high average risk (HAR) group. Offspring of men without SUD are assigned to the low average risk (LAR) group. These children are currently in varying stages of follow-up evaluation conducted at ages 12-14, 16, 19, and annually thereafter until age 30. During the next five years it is anticipated that approximately 117 subjects undergoing the age 22 assessment will have succumbed to SUD; thus, the Center is at the stage where determination of SUD liability is a feasible undertaking. Comprehensive multidisciplinary protocols are administered to family members (father, mother, children, stepparents, 1st degree relatives of father and mother) with the objective of elucidating the genetic, biobehavioral, and environmental contributors of SUD liability. These protocols are organized into four thematically connected research modules (horizontal Center integration) which accrue the data to input to the Scientific Core (vertical integration) to achieve the Center's scientific goals. The Center, having the programmatic name Center for Education and Drug Abuse Research (CEDAR), is structured in 9 components (5 cores and 4 research modules): 1) Administrative Core (R. Tarter, Ph.D., M.P.A.), 2) Scientific Core (M. Vanyukov, Ph.D.), 3) Clinical Core (J. Cornelius, M.D., M.P.H.), 4) Computing and Information Systems Core (A. Mezzich, Ph.D., M.I.S.), 5) Methodology and Statistics Core (L. Kirisci, Ph.D.), 6) Developmental Psychopathology Module (D. Clark, M.D., Ph.D.), 7) Neurocognition Module (R. Tarter, Ph.D.), 8) Genetics Module (M. Vanyukov, Ph.D.), and, 9) Family and Social Ecology Module (M. Dunn, Ph.D.). In 2007, CEDAR will have completed 13 years of prospective investigation into the etiology of SUD. During the ensuing five years, research will be directed at characterizing SUD liability, development of the individual liability index, and empirically confirm/disconfirm CEDAR's theory of SUD etiology.